Over forty years ago, Fisher and Griffin suggested that the human oral cavity could be regarded as a pharmacological preparation in situ. They proposed that the perceived bitterness intensity of a compound reflects the compound's pharmacological activity and potency. As support for this idea, they pointed out that for several drugs, the active isomer was more bitter than the inactive one. There is also a rough correlation between the bitter potency of selected toxins and their LD50 values.
In addition to the quality and intensity of a sensation, the perceived location may have pharmacological implications. Many compounds when put in the oral cavity elicit irritation (e.g., burning, stinging, cooling) and, just as for bitter taste, the irritation may serve as a signal of potential danger.
Some compounds with site-specific irritation have a beneficial effect. A desirable attribute of many premium olive oils is the distinctive irritation or pungency that is unusual because it is almost exclusively perceived on the pharynx and not in the mouth.
In 1993, Montedoro and co-workers reported the isolation of a new class of phenolic compounds (1-4), including the dialdehydic and aldehydic forms of ligstroside (5) and oleuropeine (6) from virgin olive oils (Montedoro, G. et al. (1993) J. Agric. Food Chem. 41:2228-2234) (See FIG. 1 for structures). These phenolic compounds comprise important minor constituents of virgin olive oils that have been implicated in the organoleptic characteristics including bitterness, pungency, and astringency (Andrewes, P. et al. (2003) J. Agric. Food Chem. 57:1415-1420). In addition, these agents have been suggested to contribute to the oxidative stability of virgin olive oil and as such are associated with health benefits of olive oils, specifically their antioxidant/anticancer activities (Owen, R. W. et al. (2000) Food Chem. Toxicology 38:647-659; Owen, R. W. et al. (2000) Eur. J. Cancer 36(10):1235-1247; Baldioli, M. et al. (1996) J. Am. Oil Chem. Soc. 73(11):1589-1593; Manna, C. et al. (2002) J. Agric. Food Chem. 50(22):6521-6526). Similar structural features have been reported in the constituents of the Jasminum (Somanadhan, B. et al. (1998) Planta Medica 64:246-50; Takenaka, Y. et al. (2002) Chem. & Pharm. Bull 50(3):384-389) and related plant species (Takenaka, Y. et al. (2002) Phytochemistry 59(7):779-787). It has been shown that both ibuprofen and a Mediterranean diet (i.e., high in olive oil) both decrease the risk/incidence for breast and lung cancer.
In 2003, Busch and co-workers at Unilever Research and Development Vlaardingen (The Netherlands) identified deacetoxydialdehydic ligstroside aglycone as a principal contributor to the potent pungent (burning) sensation at the back of throat associated with high quality virgin olive oils (Andrewes, P. et al. (2003) J. Agric. Food Chem. 57:1415-1420). Studies at Firmenich, Inc., reached the same conclusion (Firmenich, Inc. study). The structure of 1 was assigned,
employing a series of 1 and 2D NMR experiments (Andrewes, P. et al. (2003) J. Agric. Food Chem. 57:1415-1420), in conjunction with comparison to literature data (Montedoro, G. et al. (1993) J. Agric. Food Chem. 41:2228-2234). The absolute stereochemistry remained undetermined. That 1 was responsible for the strong pungent (burning) sensation at the back of the throat was based on an extensive series of HPLC fraction analysis, omission analysis and correlation, and hydrolysis studies, in conjunction with human sensory studies. Andrewes et al., however, acknowledged that “a coelution compound causing the burning sensation” could not be eliminated without completing a synthesis of 1, which they stated to be “extremely challenging.”